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Publication : In vitro and in vivo models define a molecular signature reference for human embryonic notochordal cells.

First Author  Warin J Year  2024
Journal  iScience Volume  27
Issue  2 Pages  109018
PubMed ID  38357665 Mgi Jnum  J:345250
Mgi Id  MGI:7595042 Doi  10.1016/j.isci.2024.109018
Citation  Warin J, et al. (2024) In vitro and in vivo models define a molecular signature reference for human embryonic notochordal cells. iScience 27(2):109018
abstractText  Understanding the emergence of human notochordal cells (NC) is essential for the development of regenerative approaches. We present a comprehensive investigation into the specification and generation of bona fide NC using a straightforward pluripotent stem cell (PSC)-based system benchmarked with human fetal notochord. By integrating in vitro and in vivo transcriptomic data at single-cell resolution, we establish an extended molecular signature and overcome the limitations associated with studying human notochordal lineage at early developmental stages. We show that TGF-beta inhibition enhances the yield and homogeneity of notochordal lineage commitment in vitro. Furthermore, this study characterizes regulators of cell-fate decision and matrisome enriched in the notochordal niche. Importantly, we identify specific cell-surface markers opening avenues for differentiation refinement, NC purification, and functional studies. Altogether, this study provides a human notochord transcriptomic reference that will serve as a resource for notochord identification in human systems, diseased-tissues modeling, and facilitating future biomedical research.
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